Altered serotonergic function of dorsal raphe nucleus in perinatally protein-deprived rats: effects of fluoxetine administration

We have previously described that perinatally undernourished rats showed increased locus coeruleus activity, a phenomenon reversed by repeated desipramine or fluoxetine administration. Since there is reciprocal modulation between the locus coeruleus and the dorsal raphe nucleus, and because these structures are associated with the pathophysiology of different states of anxiety, we evaluated the activity of serotonergic dorsal raphe neurons from early malnourished animals compared with controls, using in vivo extracellular single-unit recordings. The number of spontaneously active cells/track was significantly higher in protein-deprived animals, although the firing rate and the sensitivity of 5-HT(1A) receptors did not differ from those of controls. Five days of fluoxetine administration (5 mg/kg/day i.p.) was able to reverse the increased number of active serotonergic cells without affecting their firing rate. Furthermore, subsensitivity of 5-HT(1A) autoreceptors developed in the same way after repeated fluoxetine administration in both control and protein-deprived animals. These results suggest that the increased noradrenergic transmission observed in protein-deprived animals may induce an activation of serotonergic neurons in the dorsal raphe nucleus, and that this effect is normalized following fluoxetine treatment, which normalizes locus coeruleus activity.